Project title
1. Localisation of 5-HT1A receptors in
human brain. 2.Variability in isoform
expression patterns of tyrosine
hydroxylase in Parkinson’s disease.
Clinicopathological relationships in
patients with progressive supranuclear
palsy.
Case type
Control
Tissue supplied
Fixed
Brain regions requested
Basal Ganglia,
Brainstem
Project summary
Project one localised a receptor in the motor regions of the healthy human brain as this receptor is thought to participate
in the beneficial effects of a new drug to treat Parkinson's disease. In project two we described differences in expression
of an enzyme, which may make cells more vulnerable to death in Parkinson's disease.
Control
Fixed
Various Cortical and
Sub-Cortical Areas
Dopaminergic neurons in the olfactory
bulb in neurodegenerative diseases.
Parkinson, Alzheimer,
Frontotemporal
dementia, Control
Fixed
Olfactory Bulb
The staging and severity of multiple
system atrophy.
Control
Fixed
Basal Ganglia,
Brainstem, Cerebellum
Molecular basis of dependence in the
mesocorticolimbic system.
Alcoholic, Control
Frozen
Somatic mutations in Motor Neuron
Disease.
Motor Neuron Disease
Frozen
Analysis of gene expression and
epigenetics underlying schizophrenia.
Analysis of gene expression and
epigenetics underlying addiction
Analysis of the proteome of the BA46
prefrontal cortex region from postmortem samples of subjects affected
with schizophrenia compared to
controls.
Identification of disease-specific
molecules expressed on cerebral
endothelium - preliminary studies on
cerebral endothelium from brain tissue
not-suitable-for-research.
Protein Profiling the Human Alcoholic
Brain.
Schizophrenia,
Substance Abuse
Alcoholic, Control
Frozen
Prefrontal, Nucl.
Accumbens Amygdala,
Ventral Tegmental
Area.
Spinal Cord, Motor
Cortex, Brainstem,
Cerebellum.
Prefrontal
Most existing literature on clinicopathological correlations in progressive supranuclear palsy (PSP) only address the
relationship between clinical features and subcortical structures, as PSP is considered to be primarily a subcortical disease
of the basal ganglia. In this study we plan to analyse the relationship between cortical (particularly frontal lobe) damage
and neuropsychological features in PSP, particularly concentrating on language and visuospatial functions which have not
been previously investigated.
There have been limited neuropathological studies of olfactory bulb in the aged and in neurodegenerative diseases. It is
well established that olfactory ability declines with age. Hyposmia and anosmia (complete loss of olfaction) occur very
early in Parkinson's disease and late in Alzheimer's disease. There have been no studies regarding the integrity of the
olfactory system in frontotemporal dementia.
The parkinsonian disorders, multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), differ from
Parkinson's disease (PD) pathologically in their pattern of cell loss, type of neuronal inclusions, but particularly by their
glial inclusions. There have been limited quantitative studies demonstrating neuronal loss in only a few selected regions
in both PSP and MSA, but few of these studies have assessed any association with clinical features. In MSA clinical
correlates have been made between akinesia and cell loss in the putamen and substantia nigra, between rigidity and nigral
loss, and between cerebellar ataxia and neuronal loss in the inferior olives and the cerebellar cortex. If true these
relationships should also occur in PSP. Oligodendroglia in MSA and PSP accumulate intracellular inclusions, although
the association with neuronal degeneration has yet to be determined.
Our research aims to elucidate the molecular mechanisms underlying addiction to alcoholism and tobacco smoking. We
are investigating gene and protein expression in the dopaminergic mesocorticolimbic system of alcoholics, smokers and
control subjects.
Frozen
Prefrontal
Schizophrenia, Control
Frozen
Prefrontal
Tissue not suitable for
research
Frozen
Frontal and Temporal
The aim of this project is to identify disease-specific molecules expressed on cerebral endothelium, which can assist in
the transport of therapeutic molecules into the CNS, in Alzheimer's disease, Parkinson's disease, Creutzfeldt-Jakob
disease and multiple sclerosis.
Alcoholic, WernickeKorsakoff
Frozen
Cerebellum, BA9
Analysis of the proteome of the
hippocampal formation in
schizophrenia.
The role of Schwann cells in diabetic
peripheral neuropathy.
Schizophrenia, Control
Frozen
Hippocampus,
Parahippocampus
Diabetes
Fixed
Peripheral Nerve
Using proteomics technology, protein expression profiles of various regions of the normal post-mortem human brain will
be created and compared to alcoholic brain tissue. By identifying proteins altered in the alcoholic brain, an array of
potential markers will be developed for the characterisation of alcohol-related brain damage.
Hippocampal formation, a region critical for learning, memory consolidation and sensory gating, has been implicated in
schizophrenia (SZ) pathogenesis. We are using proteome methodology to identify differentially expressed proteins in the
anterior, posterior and parahippocampal gyrus that may underlie abnormal functioning of this region in SZ.
The role of Schwann cells in diabetic peripheral neuropathy: a pilot study using paraffin-preserved archival human
material.
In this group of experiments we are looking for evidence that DNA in the brain in motor neuron disease is different from
DNA in other tissues, i.e. that there are somatic mutations present. These differences could be either at the genetic,
chromosomal, or epigenetic level.
We examine the brain mechanism underlying schizophrenia with diversity of genetics and epigenetics. The quantitative
difference of gene expression, splicing variations, methylation on genome and RNA modification will be examined.
The aims of the studies are to find the brain mechanism underlying vulnerability for addiction. We compare the
quantitative and qualitative difference in genetics and in epigenetics between cases and controls
The BA46 region has been implicated in working memory deficit and abnormal activation of this region has been
observed in schizophrenia patients. We are using proteomics approach to identify proteins differentially expressed in the
grey and white matter that may underlie abnormal function of the BA46 region.
Proteomics in the Hippocampus of
Alcoholic Human Brain.
Alcoholic, Substance
Abuse, Cirrhosis,
Control
Schizophrenia, Control
Frozen
Hippocampus
Analysis of protein expression profile in the hippocampus of alcoholic human brains using proteomics-based approach.
Frozen
BA9, Temporal
Control
Frozen
Motor Cortex White
Matter
The roles of adrenoceptors and the
intracellular signal transduction proteins
in the aetiology of schizophrenic
symptoms.
Investigation of PARK and associated
gene mutations and polymorphisms in
autopsy confirmed Lewy body diseases.
The neuropathology of white matter
hyper-intensities.
Schizophrenia, Bipolar
Disorder, Control,
Depression
Frozen
BA9, Visual
We are investigating the changes to gene expression in post-mortem brains in schizophrenia and controls to better
understand what causes the disorder.
Multiple system atrophy (MSA) is pathologically characterised by the abnormal deposition of alpha-synuclein in both
neurons (also occurs in other neurodegenerative diseases) and oligodendroglia (unique to MSA). Alpha-Synuclein is not
normally found in oligodendroglia (Gai et al., 1999), and the intracellular changes to critical oligodendroglial proteins
that must occur due to this abnormal process have not been explored
This study will investigate the expression of adrenoceptors and their respective intracellular signal transduction proteins
in schizophrenia.
Parkinson
Frozen and
Fixed
Occipital Pole
LRRK2 mutations account for 5% of familial and 2% of sporadic Parkinson's disease (PD). We aim to screen
pathological cases of PD for LRRK2 gene mutations to understand any differences in pathological phenotypes.
Specified cases
Fixed
Periventricular & Deep
White Matter
International collaboration to perform a
genome wide association study in
autopsy confirmed frontotemporal lobar
degeneration with ubiquitin inclusions.
Frontotemporal
Dementia, Control
Frozen
Cerebellum, Cortex
Mechanisms of neurodegeneration and
cognitive impairment induced by
alcohol: development of
neuroprotective pharmacotherapy.
Alcoholic, Control
Frozen
Hippocampus,
Prefrontal
Changes in proteomics of brain in
schizophrenia.
Schizophrenia, Control
Frozen
BA17, BA9, Caudate.
Impaired insulin signalling in brains of
chronic alcoholics.
Alcoholic, Control
Frozen and
Fixed
Cerebellum, Cingulate.
Alzheimer risk and polymorphisms of
the folate/ methionine pathway.
A novel physiological role for
cytochrome P450 enzymes in the brain?
Control
Frozen
Hippocampus
Tissue not suitable for
research
Frozen
Membrane phospholipid composition in
superior temporal gyrus (STG) of
schizophrenia brain.
Schizophrenia and Neuropathology of
Amygdala.
Membrane phospholipid composition
Schizophrenia, Control
Frozen
Frontal, Hippocampus,
Amygdala, Basal
Ganglia
Temporal Lobe
The pathological substrate of white matter hyper-intensities (WMH), a common finding on MRI scans of elderly
individuals, is unknown. In this study WMH will be investigated histopathologically using a number of markers of
vascular integrity.
Research has shown that one of the most common pathologies underlying the clinical features of frontotemporal dementia
is frontotemporal atrophy with ubiquitin-positive inclusions (FTD-U). The protein/s at the heart of the ubiquitinated
inclusions in this disease remains a mystery, even though there is a current world-wide effort to determine their identity.
For other neurodegenerative disorders significant clues concerning the proteins involved and their critical processing
pathways in the brain have been determined by focusing on genetic determinants. Although FTD-U is a rare disorder, Dr
Pickering-Brown’s request to international colleagues currently publishing in the field for the numbers of available
autopsy confirmed cases with DNA has determined that 240 FTD-U cases are available world-wide for genetic analyses.
As only 20-30% of these cases have a family history of disease, the approach considered most appropriate for genetic
analysis of FTD-U is a genome-wide association study. We will participate in this study by contributing sporadic and
unique familial cases
Our project is focused on transcriptional and cellular mechanisms of neurodegeneration in the human brain in association
with alcohol abuse. We found that the NF-kappa B system critical for neuroplasticity and neurodegeneration is
dysregulated whereas alterations in the cell suicide machinery contribute to presynaptic injury in the PFC in chronic
alcoholics. These adaptations apparently contribute to cognitive impairment associated with alcoholism, and to alcohol
dependence.
We investigate changes in brain protein expression profiles due to schizophrenia and antipsychotic drugs. The identified
proteins will point out on molecular mechanisms for the disease pathogenesis and on potential targets for novel drugs
development.
The TRC makes available, human alcoholic brain tissue that is in excellent condition and suitable for performing
molecular and biochemical studies. Through analysis of the human tissue samples, we were able to determine the degree
to which the impairments in insulin signalling observed in experimental rat models of chronic alcohol feeding also occur
in human subjects. The research data provided us with new information about how alcohol mediates its adverse effects
on brain function.
To investigate DNA damage markers and genotyping of polymorphisms within the folate /methionine pathway in
Alzheimer patients and in gender and age matched controls.
This project involves the characterisation of cytochrome P450 distribution in various regions of the brain. This work is
directed towards defining the involvement of these enzymes in metabolism of indole in the human brain.
Schizophrenia, Control
Frozen
Amygdala
Schizophrenia, Control
Frozen
Anterior Cingulate
Gene Expression Profiling in
Schizophrenia.
Investigating changes in myelin
associated proteins in multiple system
atrophy (MSA).
We examined membrane phospholipid composition and neurotransmitter receptor density in the superior temporal gyrus
of schizophrenia and control subjects. It was found that there is increased GABAa and reduced muscarinic M1 and M2/4
receptor binding in the STG in schizophrenia.
The aim of this project was to investigate the neuronal alterations in the amygdala that are correlated with schizophrenia.
This project examined size, shape, and density of brain cells in the amygdala of control and schizophrenia cases.
This study examined membrane phospholipid composition and serotonin binding in the anterior cingulate cortex in
and 5HT binding efficiency in
schizophrenia.
Autoimmunity in Schizophrenia.
schizophrenia. Altered membrane phospholipid composition and serotonin binding was found.
Schizophrenia, Control
Fixed
Hippocampus, BA9
Proteomics of human post-mortem
brain.
Analysis of the proteome of the corpus
callosum from post mortem samples of
subjects affected with schizophrenia
compared with controls.
3D Golgi analysis of the prefrontal
cortex and hippocampus in
schizophrenia/ Immunohistochemical
analysis for chromogranin A and B
expression in schizophrenia brains.
Immunohistochemical analysis for
chromogranin A and B expression in
schizophrenia brains.
The expression of hNP22 in the frontal
cortex, the hippocampus and anterior
cingulate cortex of schizophrenia.
Investigation of the role of the posterior
cingulate cortex as an anatomical locus
of disturbed neural circuitry in
schizophrenia.
Glutamate transporters in human
hippocampus: alterations in
schizophrenia.
Alcoholic, Control
Frozen
Hippocampus
Schizophrenia, Control
Frozen
Corpus Callosum
Schizophrenia, Control
Fixed
Prefrontal,
Hippocampus
Significant decrease of chromogranin A expression was observed in the brain of schizophrenia. 3D Golgi staining was not
stable enough to be used to analyse this type of brain tissue.
Schizophrenia, Control
Fixed
Prefrontal,
Hippocampus
Significant decrease of chromogranin A expression was observed in the brain of schizophrenia.
Schizophrenia, Control
Fixed
Frontal, Hippocampus,
Anterior Cingulate
Significant decrease of hNP22 expression was observed in the brain of schizophrenia.
Schizophrenia, Control
Fixed
Posterior Cingulate
This project examines neurotransmitter receptors in the posterior cingulate cortex in schizophrenia. To date, we have
found specific alterations in glutamatergic, cholinergic, gaba-ergic, serotonergic and cannabinoid systems in this brain
region in schizophrenia subjects compared to controls
Schizophrenia, Control
Fixed
Hippocampus, Visual
Understanding the molecular basis of
bipolar affective disorder.
Schizophrenia,
Alcoholic, Control
Frozen
Cerebellum
Tachyninin receptors in human brain.
Schizophrenia, Control
Amygdala
Investigate neurological basics of
schizophrenia.
Molecular cell biology of hNP22: role
in alcohol dependence-Amygdala,
VTA, NA, PFC.
Molecular mechanisms of abnormal
acetylcholine neurotransmission in
schizophrenia
Entorhinal Transcriptome of
Schizophrenia
Schizophrenia, Control
Fixed and
Frozen
Frozen
We have investigated whether there were changes in glutamate transporter expression in the human hippocampus in
schizophrenia. We have used a panel of antibodies to examine if there are anomalies in astrocytes in this region. Our
findings suggest that there is no clear evidence for an overall anomaly in glutamate regulating proteins but here may be
some subtle idiosyncracies.
Using tissue from the Australian Brain Donor Programs we have been able to examine the nature of the expression
patterns, mRNA splicing, etc of a recently identified bipolar disorder susceptibility gene, the protocadherin FAT. The
study is also examining other genes that have altered expression in response to the FAT susceptibility alleles.
Investigation of the localisation of tachykinin receptors in the human brain and comparison with schizophrenia.
Alcoholic, Control
Frozen
Schizophrenia, Control
Frozen
Amygdala, Ventral
Tegmental Area, Nucl.
Accumbens, Prefrontal
Caudate-Putamen
Schizophrenia, Control
Frozen
Entorhinal
Proteomics of the nucleus accumbens in
schizophrenia and substance use in
schizophrenia.
Schizophrenia, Control
Frozen
Nucleus Accumbens
Follow-on project to look at p25α
Controls
Frozen
Pons
Posterior Cingulate
My project involves looking for antibodies against the brain in the serum of people with schizophrenia. Using human
brain tissue samples and commercial antibodies to selected neurotransmitter receptors we have established that the
receptors are the same in people with schizophrenia and healthy controls, but that the levels of receptors are different. We
are now screening serum samples for antibodies.
We have compared the protein expression pattern between two different regions of the normal human brain white matters
(BA9 vs CC). It will show the heterogeneity among the white matters.
Abnormalities within the corpus callosum are thought to affect inter-hemispheric communication and this in turn may
underlie some of the schizophrenia symptoms. We are applying proteomics approach to identify differentially expressed
proteins that may underlie these abnormalities.
Compare neuronal and glial cell densities within the posterior cingulate, between people who suffered with schizophrenia
and controls
Our research aims to elucidate the molecular mechanisms underlying addiction to alcoholism and tobacco smoking. We
are investigating the RNA and protein expression of a novel alcohol-responsive gene in various tissue.
The role of the caudate-putamen in the pathophysiology of schizophrenia is not well understood. In this project, we aim to
reveal the molecular mechanisms of abnormal acetylcholine and GABA neurotransmissions in the caudate-putamen in
schizophrenia.
This project will compare glutamate receptors and related mRNAs and proteins in the entorhinal cortex of individuals
diagnosed with schizophrenia with matched controls. Similar assessments will be made of the entorhinal cortex of rhesus
monkeys treated chronically with the antipsychotic medications clozapine and haloperidol.
Using proteomic analysis, we will identify the differentially expressed proteins in the nucleus accumbens in the brain of
subjects with schizophrenia and animal models of developmental vitamin D deficiency (DVD) and chronic antipsychotic
treatment. Co-operating the data from both animal models with findings in humans will allow us to identify specific
changes in protein expression in nucleus accumbens in schizophrenia.
In a preceding study on multiple system atrophy (MSA) we found that p25a relocalizes in oligodendroglia prior to
phosphorylation
Synchrotron microprobe analysis and
speciation of trace metals in
neuromelanin in the healthy and
parkinsonian brain.
Preservation of neurochemical
substances in postmortem brain tissue
Parkinson, Control,
Incidental Lewy Body,
Alzheimer
Fixed
Caudate, Putamen,
Ventral Tegmental
Area, Midbrain, Pons
Controls
Frozen
Cingulate, Frontal,
Striatum, Cerebellum
Differential regulation of human
tyrosine hydroxylase isoforms and the
development of Parkinson’s disease
Distribution of brain pigments in the
healthy brain and in Parkinson’s disease
Parkinson, Control
Fixed
Ventral Tegmental
Area, Midbrain, Pons
Control
Frozen
Frontal, Midbrain
New therapeutic approaches for ALS
based on ER stress and induction of the
UPR.
Gene expression in the human alcoholic
brain
Control
Frozen
Cervical Spinal Cord
Alcoholic, Control
Frozen
Amygdala, Frontal
Protein expression of the nicotinic
receptors in the human adult and infant
brainstem and hippocampus using
immunohistochemistry.
Molecular mechanisms of abnormal
acetylcholine neurotransmission in
schizophrenia
Analysis of Neuroinflammatory
markers in human alcoholic brain
Control
Fixed
Midbrain, Pons,
Hippocampus
Schizophrenia, Control
Frozen
Basal Forebrain
Alcoholic, Control
Frozen
Alcohol dependence: integrating
genetic and fMRI methods
Alcoholic, Control
Frozen
Brain glucocorticoids and alcohol:
mechanisms
Functional studies of variants in the
muscarinic acetylcholine receptor
M2(CHRM2) that demonstrate
association with alcohol dependence,
depression and related phenotypes
The roles of α- and β-adrenoceptors,
and the intracellular signal transduction
proteins in the aetiology of
schizophrenic symptoms.
Gene Methylation and Schizophrenia
Alcoholic, Control
Frozen
Alcoholic, Control
Frozen
Hippocampus,
Midbrain, Ventral
Tegmental Area,
Amygdala
Ventral Tegmental
Area, Prefrontal,
Nucleus Accumbens
Frontal, Hippocampus,
Cerebellum
Prefrontal
Schizophrenia,
Control, Depression
Frozen
Anterior Cingulate
Schizophrenia, Control
Temporal
Relation between dopamine, GABA
and glutamate receptors in the anterior
Schizophrenia, Control
Frozen and
Fixed
Fixed
Anterior Cingulate,
Temporal
disease-associated intracellular protein accumulation. This study will use proteomic techniques to identify posttranslation
modifications (eg. phosphorylation) on p25a in normal and diseased brain tissue, and analyse whether disease associated
modifications can reveal pathogenic signalling pathways.
This project using a highly sophisticated technology, the synchrotron microprobe, to investigate differences in chemical
elements in the brains of persons who died with Parkinson’s disease and healthy controls. This information is hoped to
increase our understanding of why a small brain region, called the substantia nigra, is particularly vulnerable to brain cell
death in Parkinson’s disease.
Postmortem brain tissue used for research often has poor clinical characterisation, particularly regardingagonal state. We
proposwe to standardise the measurement of levels of neurochemicals such as tryptophan, phosphofructokinase, GAD
and caspase-3 along with tissue pH in control cases with and without terminal hypoxic/ischaemic insult in order to find
correlations that may improve quality control and case selection for the tissue banking community.
This project investigates the distribution and regulation of tyrosine hydroxylase, the rate limiting enzyme for the
production of dopamine and possible changes in these factors in Parkinson’s disease. Identified changes may explain the
relative selective vulnerability of the dopamine-producing cells in the midbrain in this disorder.
This project will characterise the apparent differential distribution of different brain pigments in the healthy brain and
identify changes to these pigments in different brain regions in Parkinson’s disease. This information will increase our
understanding of the physiological roles of these pigments in health and disease.
We aim to assess human ALS patient spinal cords for the presence of ER stress markers proteins in comparison to normal
controls. Evidence of ER stress and induction of the unfolded protein response provides new therapeutic targets for ALS.
Chronic alcohol abuse produces persistent changes in brain function that are manifested as tolerance, physical
dependence, craving, and other behavioral changes. We are testing the hypothesis that patterns of brain gene expression
can identify novel functional pathways that are altered in alcoholics
Comparative protein expressions of the nicotinic receptors with age in the human brainstem and hippocampus using
immunohistochemistry.
cingulate cortex and superior temporal
gyrus of schizophrenia
Involvement of the kynurenine pathway
in Alzheimer’s disease
Localisation of galanin peptides and
galanin receptors in human brain
Neuropathological changes in SID’s
infants and associations with known
clinical risk factors.
Molecular genetic analysis of functional
psychosis using postmortem brains
An investigation of the role of
alterations in soluble tau in the
neurodegeneration of frontotemporal
dementia subtypes.
DNA microarray analysis of
hypothalamus in patients with bipolar
disorder.
Amino Acid Neurotransmission In
Human Chronic Alcoholism.
Alzheimer, Control
Fixed
Control
Fixed
Alzheimer
Fixed
Schizophrenia, Control
Frozen
Frontotemporal
dementia
Frozen
Schizophrenia,
Control, Bipolar
Fixed and
Frozen
Anterior Hypothalamus
In this study, DNA microarray analysis will be performed in the hypothalamus of patients with bipolar disorder to
identify the neuronal systems responsible for bipolar disorder.
Alcoholic cirrhosis
Frozen
Frontal, Motor
Gene Expression in Human
Brain/Collaborative Study on the
Genetics of Alcoholism
Alcoholic, Control
Frozen
Somatic mutations in ALS
Motor Neuron
Disease, Control
Motor Neuron
Disease, Control
Frozen
Prefrontal, Visual,
Cingulate, Thalamus,
Caudate, Hippocampus,
Amygdala, Putamen,
Cerebellum
Prefrontal
To determine the effect of chronic alcoholism on the levels of glutamate and GABA neurotransmitter receptors in the
human brain with particular consideration of an individuals genotype. It is hoped that this will further our knowledge of
the molecular mechanisms behind alcoholic brain damage and the genetic factors that could increase our susceptibility to,
not only becoming alcoholic but also, the damage alcoholism can cause.
To characterize differences in expression of genes associated with alcohol dependence and related phenotypes as a
function of genotypes and haplotypes, in specific brain regions.
Assessment of cortical atrophy in MND
Motor Neuron Disease
Photographs
Differential regulation of human
tyrosine hydroxylase isoforms and the
development of Parkinson’s disease.
Control
Frozen
Characterisation of Schizophrenia
associated genes using a model of
antipsychotic drug action.
Somatic mutations in ALS
Schizophrenia, Control
Characterization of NSW TRC
Schizophrenia cohort
Characterising the phenotypes of a
novel causative dementia gene.
Somatic mutations in ALS
Pre-freezing
and Frozen
Hippocampus,
Temporal
Midbrain, Pons,
Cerebellum
Hippocampus
Hippocampus, BA9,
BA17.
Temporal
Prefrontal Cortex and
White Matter, Putamen,
Motor, Occipital,
Spinal Cord
Whole Brain
Frontotemporal dementia (FTD) is a spectrum of disorders characterized by a heterogeneous range of clinical phenotypes
and pathologies the cause of which is unknown. The aim of this project is to determine whether alterations to soluble tau
form a common mechanism of neurodegeneration across the range of FTD subtypes.
We are collecting brain DNA from patients with sporadic MND and from controls to see if any differences in genotype or
gene copy number can be detected using whole-genome analyses.
We are analysing brain DNA from patients with sporadic MND and from controls to see if any differences in genotype,
epigenetic or gene copy number can be detected using whole-genome analyses.
Clinical signs of MND are often observed in cases of FTD, and vice versa. This project aims to contribute to the debated
view that these be regarded as a spectrum of diseases, by determining if there are any similarities in the patterns of gross
atrophy between FTD and MND
This project investigates the distribution and regulation of tyrosine hydroxylase, the rate-limiting enzyme for the
production of dopamine and possible changes in these factors in Parkinson’s disease. Identified changes may explain the
relative selective vulnerability of the dopamine-producing cells in the midbrain in this disorder.
Frozen
Prefrontal, Substantia
Nigra, Ventral
Tegmental Area,
Caudate, Putamen
Prefrontal
Parkinson’s Disease
Frozen
Prefrontal
Schizophrenia, Control
Frozen
Prefrontal
Frontotemporal
dementia, Alzheimer,
Control
Paraffin
Frontal, Hippocampus
We plan to analyse brain DNA from patients with sporadic ALS and compare these to controls (people with Parkinson
disease and people with no neurodegenerative disease) to see if genetic differences can be detected that could be
responsible for ALS.
We will characterize the University of Sydney TRC cohort of about 32 patients with schizophrenia compared to 32
matched controls for gene expression studies in postmortem human brain.
A novel causative gene for dementia and motor neuron disease has recently been identified. This study will investigate
the role of the gene protein product in the characteristic pathological protein deposits found in frontotemporal dementia
and Alzheimer’s disease, to aid in identification of potential intracellular partners interacting with this protein.
Gene Expression Profiling in
Schizophrenia
A comprehensive methylation analysis
of 1p and 19q in oligodendrogliomas.
Schizophrenia, Control
Frozen
Control
Frozen
The contribution of cerebrovascular
disease to Parkinson’s disease.
Lewy body disease,
Control
Paraffin
Frontal, Motor, Basal
Ganglia
Neuropathological assessment of
human hypothalamic tissue from
patients with Huntington disease and
controls.
The kynurenine pathway and
inflammation in ALS.
Huntington’s, Control
Fixed
Hypothalamus
Motor Neuron
Disease, Control
Paraffin
Motor, Spinal cord.
MCP-1 in Alzheimer's disease
Control
Paraffin
Temporal
Differential Composition of Methionine
Synthase in Brain.
Alcoholic, Control
Fixed and
Frozen
Cingulate, Cerebellum
Aquaporin 1 and 4 in paediatric brain
tumours: role in oedema and
infiltration.
The overlap between FTD and other
neurodegenerative disorders.
Control
Frozen
Cerebral
Frontotemporal, Lewy
body disease,
Alzheimer, Control
Motor Neuron Disease
Paraffin
Hippocampus, Frontal
Frozen
Frontal, Spinal Cord
Neuregulin-ErbB4 pathway in
schizophrenia.
Characterisation of a new gene that
causes FTD and MND.
Schizophrenia, Control
Frozen
Prefrontal
Control
Frozen
Frontal
Molecular Actions of Alcohol and
Smoking on the Drug Reward Pathway
of the Brain
Inflammation in the pathogenesis of
FTD.
Alcoholic, Control
(smoker and non
smoker)
Frontotemporal
dementia, Pick’s
Control, Corticobasal
degeneration,
Haemorrhagic stroke,
Alzheimer
Frozen
Prefrontal, Accumbens,
Ventral Tegmental
Area
Temporal
Somatic mutations in ALS
Amyloid deposition in stroke in the
human brain.
Paraffin
Fixed
Prefrontal, Superior
Temporal
DNA
Region of Stroke,
Temporal, Frontal,
Parietal
We are investigating gene expression profiles in a number of brain regions in subjects with schizophrenia in an effort to
further the understanding of what causes this disorder.
This project will perform, for the first time, a comprehensive analysis of the methylation status of all gene promoters in
the chromosomal locations 1p and 19q in oligodendrogliomas. One copy of these genes is already lost in most
oligodendrogliomas and our hypothesis is that the second copy of genes involved in oligodendroglioma formation are
silenced by methylation of their promoters. By studying the methylation status of genes in these locations in a large group
of oligodendrogliomas we hope to identify tumour suppressor genes whose existence in these locations has long been
suspected but not yet proven.
Small vessel cerebrovascular disease (SVD) is a common finding in the elderly where it is often associated with
parkinsonism, however whether SVD also contributes to the movement disorder in patients with Lewy body disease is
unknown. This project will examine the distribution and severity of SVD in patients with Lewy body disease and
establish any correlation with severity of parkinsonism.
Changes indicative of disturbed hypothalamic function occur early in Huntington’s disease, including increased energy
metabolism, weight loss, disruption of circadian rhythm and sleep changes. This project will determine whether there is
substantial hypothalamic pathology in Huntington's disease using stereological methods.
The focus is on inflammation profile and so the AD tissue is compared with control and cases with other
neurodegenerative diseases with and without neuroinflammation. The kynurenine pathway is a significant pathway in
microglial and macrophage immune response”.
This project investigates inflammatory cytokine and chemokine expression (MCP-1, IL-6 and IL-8) in Alzheimer’s
disease brain tissue compared to age-matched controls
Previous studies indicate alternative splicing of methionine synthase mRNA in brains of elderly (>70 yrs) but not younger
(<30 yrs) individuals, and ethanol inhibits methionine synthase activity. This project will evaluate the splicing status of
methionine synthase mRNA in brain samples from alcoholic subjects vs. normal, age-matched controls.
Our research aim is to quantify and map the expression of AQP1 and 4 in samples of paediatric brain tumours. We also
will investigate the relationship of AQPs expression with tumour-related brain oedema and tumour cell migration and
dissemination.
The prevalence of FTD in the elderly is not known and until recently it was not possible to detect tau-negative FTD when
it overlaps with other pathologies. This study will use TDP-43 staining to detect FTD in patients whose dementia onset is
over 65 years.
This group will analyse DNA from laser-dissected cells in sporadic ALS spinal cord to see if we can detect mutations in
ALS candidate genes.
The Schizophrenia Research Institute collaborative project aims to understand the relationships among causative and
consequential factors of the NRG1-ErbB4 pathway in the brains of patients with schizophrenia.
We have identified a new gene that causes familial frontotemporal dementia (FTD) and motor neuron disease (MND) in
pedigrees affected with dementia and/or MND. This project will study the expression and function of this new FTD/MND
gene to determine its role in the aetiology and pathology of this complex of neurodegenerative disorders.
This project aims to characterise alcohol- and smoking-sensitive molecular pathways, which result in structural
remodelling in core regions of the mesolimbic system of the alcoholic and smoker. This pathway has a high potential to
identify novel pharmaceutical targets for alcohol and nicotine addiction.
This study investigates the contribution of inflammatory processes in FTD. Information about the mechanisms involved
in FTD will contribute to our understanding of the pathogenesis and progression of this debilitating disease. Collectively,
studies such as this facilitate future development of therapeutic strategies aimed at slowing or preventing disease
progression.
We will test whether the deposition of beta-amyloid occurs at the site strokes of different sizes in the aging brain. The
value of these observations arises from recent evidence that amyloid-rich plaques considered Alzheimer-like dementias
form at the site of bleeding. We are testing the hypothesis that bleeding precipitates the deposition of insoluble forms.